Cycloserine and threo-dihydrosphingosine inhibit TNF-alpha-induced cytotoxicity: evidence for the importance of de novo ceramide synthesis in TNF-alpha signaling.

Autor: Meyer SG; Institut für Physiologische Chemie, Universitätsklinikum Essen, Hufelandstrasse 55, D-45147 Essen, Germany. sybille.meyer@uni-essen.de, de Groot H
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta [Biochim Biophys Acta] 2003 Dec 07; Vol. 1643 (1-3), pp. 1-4.
DOI: 10.1016/j.bbamcr.2003.10.002
Abstrakt: Measuring the cell death induced by tumor necrosis factor (TNF-alpha) in L929 cells, we discovered for the first time that L-cycloserine, an established inhibitor of serine palmitoyltransferase, as well as DL-threo-dihydrosphingosine (threo-DHS, threo-sphinganine) significantly protected against TNF-alpha-induced cytotoxicity. Under the same conditions sphingosine and DL-erythro-dihydrosphingosine (erythro-DHS) did not change TNF-alpha-induced cytotoxicity, thus underlining the specificity of threo-DHS. In serine-labeled cells, newly (de novo) synthetized labeled ceramide was significantly diminished by threo-DHS alone or together with TNF-alpha, which makes the (dihydro) ceramide synthase the likely target of threo-DHS. These results suggest the decisive role of ceramide de novo synthesis in TNF signaling.
Databáze: MEDLINE